U.S. patent application number 13/496184 was filed with the patent office on 2012-07-12 for nasal, wound and skin formulations and methods for control of antibiotic-resistant staphylococci and other gram-positive bacteria.
Invention is credited to B. Eugene Guthery.
Application Number | 20120178731 13/496184 |
Document ID | / |
Family ID | 43759291 |
Filed Date | 2012-07-12 |
United States Patent
Application |
20120178731 |
Kind Code |
A1 |
Guthery; B. Eugene |
July 12, 2012 |
NASAL, WOUND AND SKIN FORMULATIONS AND METHODS FOR CONTROL OF
ANTIBIOTIC-RESISTANT STAPHYLOCOCCI AND OTHER GRAM-POSITIVE
BACTERIA
Abstract
Formulations and methods are disclosed which are effective to
kill or control bacteria in the nares including gram-positive
bacteria strains of S. aureus that are antibiotic resistant
(MRSA--methicillin-resistant Staphylococcus aureus. A preferred
composition comprises one or more medium-chain alcohols
(dodecanol), glycerol monoesters (glycerol monocaprylate or
glycerol monolaurate), and/or benzoic acid or benzoic acid analog,
in a suitable pharmaceutical carrier, preferably an ointment, along
with an odorant compound, preferably eucalyptus oil. The
formulations and variations of the formulation may also be used on
open wounds or lesions as well as intact skin.
Inventors: |
Guthery; B. Eugene;
(Texarkana, TX) |
Family ID: |
43759291 |
Appl. No.: |
13/496184 |
Filed: |
September 17, 2010 |
PCT Filed: |
September 17, 2010 |
PCT NO: |
PCT/US2010/049336 |
371 Date: |
March 14, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61243455 |
Sep 17, 2009 |
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61257922 |
Nov 4, 2009 |
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Current U.S.
Class: |
514/188 ;
514/552 |
Current CPC
Class: |
A61L 2300/22 20130101;
A61L 26/009 20130101; A61L 2300/404 20130101; A01N 31/02 20130101;
A61L 26/0023 20130101; A61L 2300/216 20130101; A01N 31/02 20130101;
A61K 31/23 20130101; A61L 26/0047 20130101; A61K 31/23 20130101;
A61P 31/04 20180101; A61K 31/045 20130101; A61K 31/045 20130101;
A61L 15/46 20130101; A61L 2300/45 20130101; A61L 15/38 20130101;
A01N 31/02 20130101; A61L 26/0066 20130101; A01N 31/02 20130101;
A61P 17/00 20180101; A61K 9/0043 20130101; A01N 37/02 20130101;
A01N 37/02 20130101; A01N 37/10 20130101; A01N 2300/00 20130101;
A01N 37/10 20130101; A01N 2300/00 20130101; C08L 5/08 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 31/185 20130101; A61K 31/185 20130101; A61L 26/0023
20130101; A61K 9/0014 20130101; A61K 9/06 20130101; A61L 27/227
20130101; A01N 37/02 20130101 |
Class at
Publication: |
514/188 ;
514/552 |
International
Class: |
A61K 31/555 20060101
A61K031/555; A61P 31/04 20060101 A61P031/04; A61K 31/23 20060101
A61K031/23 |
Claims
1. A method of treating a patient in need of treatment to reduce or
eliminate the concentration of antibiotic-resistant bacteria
colonized on said patient, comprising applying a formulation
comprising a C9 to C12 aliphatic alcohol and a C10 to C13 fatty
acid glycerol ester to a site of bacterial colonization on said
patient.
2. The method of claim 1, wherein said aliphatic alcohol is C10 to
C12.
3. The method of claim 2, wherein said aliphatic alcohol is
C12.
4. The method of claim 1, wherein said fatty acid glycerol ester is
a glycerol monoester.
5. The method of claim 4, wherein said glycerol monoester is
selected from the group consisting of glycerol monolaurate,
glycerol monocaprin, and glycerol monocaprylate.
6. (canceled)
7. (canceled)
8. The method of claim 1, wherein said formulation further
comprises an organic acid.
9. The method of claim 8, wherein said organic acid is benzoic
acid.
10. The method of claim 1, wherein the antibiotic-resistant
bacteria are strains of MRSA (methicillin-resistant Staphylococcus
aureus).
11. (canceled)
12. A method according to claim 1, wherein said site of bacterial
colonization is selected from the group consisting of the nares and
intact skin.
13. A method according to claim 1, wherein said site of bacterial
colonization is a wound or skin lesion.
14. A method according to claim 1, wherein said formulation further
comprises a penetrating agent.
15. The method according to claim 1, wherein said formulation
further comprises a botanical oil as an odorant.
16. The method of claim 15, wherein said botanical oil is
Eucalyptus Oil.
17. A formulation for application to the human nares for reducing
the concentration of antibiotic-resistant bacteria thereon,
comprising a C9 to C12 straight chain alkyl alcohols, a C10 to C17
fatty acid glycerol ester, a penetrating agent, and a carrier
ointment.
18. The formulation according to claim 17, wherein said alcohol is
C12 dodecanol.
19. The formulation of claim 18, wherein the fatty acid glycerol
ester is selected from glycerol monocapric acid, glycerol
monocaprylate, and glycerol monolaurate.
20. A method according to claim 12 for rapidly eliminating
antibiotic-resistant bacteria from the nares of a human patient,
comprising topical application of said formulation to said nares,
wherein said aliphatic alcohol is dodecanol in an amount of 10% or
less.
21. The method of claim 20, wherein said fatty acid glycerol ester
is glycerol monolaurate.
22. The method of claim 20, further comprising upon topical
application to said nares for at least about one minute, whereby a
greater than seven log kill of antibiotic resistant bacteria
occurs.
23. (canceled)
24. A formulation to reduce or eliminate gram positive bacteria,
comprising a C9 to C12 alcohol and a fatty acid ester selected from
glycerol monocapric acid, glycerol monocaprylate, and glycerol
monolaurate.
25. The formulation of claim 24, further comprising an organic
acid.
26. The formulation of claim 24, wherein said organic acid is
benzoic acid.
27. The formulation of claim 24, wherein the topical formulation
comprises an iodophore.
28. The formulation of claim 24, further comprising a persistent
agent selected from the group consisting of zinc pyrithione,
chlorhexidine and triclosan.
29. The formulation of claim 24, further comprising a C2 to C3
alcohol.
30. (canceled)
31. (canceled)
32. (canceled)
33. The formulation of claim 24 adapted for use as an adjuvant for
enhancing the effectiveness of a second topical formulation.
34. The formulation of claim 29 adapted for use as a hand and body
wash.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application 61/243,455 filed 17 Sep. 2009 and U.S. Provisional
Application 61/257,922, filed 4 Nov. 2009.
TECHNICAL FIELD
[0002] This invention relates to the field of treating humans
colonized or infected with antibiotic-resistant gram-positive
bacteria.
BACKGROUND OF THE INVENTION
[0003] Antimicrobial resistance occurs when bacteria change or
adapt in a way that allows them to survive in the presence of
antibiotics designed to kill them. In some cases bacteria become so
resistant that no available antibiotics are effective against them,
and such resistance limits or even eliminates the therapeutic
options. Gram-positive bacteria such as Staphylococcus aureus and
Enterococcus faecalis are particularly problematic because they can
cause a range of diseases including skin lesions, bacteremia,
sepsis, pneumonia, endocarditis and osteomyelitis. Skin lesions can
easily progress to life-threatening blood or bone infections. Some
strains of antibiotic-resistant S. aureus also produce the
destructive Panton-Valentine leukocidin toxin.
[0004] One of the bacteria discussed above, Staphylococcus aureus
has long been recognized as particularly problematic as a pathogen
in human diseases. Staphylococcal infections occur regularly in
hospitalized patients. In recent years, an increasing number of
these infections are caused by Methicillin-resistant Staphylococcus
aureus (MRSA) strains, which are most often resistant to multiple
antibiotics. MRSA has become a major nosocomial pathogen in many
hospitals worldwide and has also become a leading cause of
colonization and infection in both acute and chronic soft-tissue
wounds. MRSA also is increasingly an active pathogen outside the
hospital setting.
[0005] Three types of MRSA are currently recognized: [0006]
HA-MRSA--(HA--hospital acquired) Methicillin resistant
Staphylococcus acquired in hospitals or healthcare facilities,
including in such facilities as nursing homes and dialysis centers
[0007] CA-MRSA--(CA--community acquired) Methicillin resistant
Staphylococcus acquired in a community setting, [0008] USA 300--A
community acquired strain which is not only resistant to
Methicillin, but is also resistant to Vancomycin. This strain is
found most prevalently in schools, prisons, among athletic teams,
and within the homosexual community.
[0009] Frequently wounds and skin lesions become infected with MRSA
by transfer of organisms from the nasal passages to the wound via
the hands. Wounds may also become infected by the introduction of
MRSA from community-acquired MRSA sources. This may occur when an
individual has the skin colonized with the CA-MRSA strain or
USA-300 strain if the skin integrity is broken through minor trauma
or from vascular insufficiency due to, for example, diabetes.
[0010] It is important to note that all three types of MRSA can be
spread by human to human contact, or animal to human contact, and
may exhibit different epidemiology.
[0011] The difference between MRSA and methicillin-susceptible S.
aureus (MSSA) is resistance to .beta.-lactamase-stable
.beta.-lactam antibiotics. MRSA strains that are resistant to
.beta.-lactam antibiotics and other antibiotics have generally
maintained a high level of in vitro susceptibility to vancomycin,
although slight changes with in vitro activity could vastly change
clinical activity. As a result, vancomycin has become the mainstay
of therapy for invasive infections due to MRSA strains.
Unfortunately, clinical strains of S. aureus with intermediate
resistance to vancomycin were reported in 1996, followed in 2002
with reports of isolates that were fully resistant. As use of
vancomycin increases, the probability of resistance increases as
well. Over-prescribing of antibiotics is recognized as a key factor
in the development of resistance. The Center for Disease Control
has even begun a campaign to prevent antimicrobial resistance which
teaches the judicious use of antimicrobials while particularly
avoiding the overuse of broad-spectrum antibiotics with the hope of
stemming the increased prevalence of antibiotic resistance.
[0012] One of the most prevalent ecological niches of S. aureus
strains and other gram-positive pathogenic bacteria is the anterior
nares. Epidemiology indicates that organisms often spread from the
nose to other parts of the body through human behavior. For
example, children often wipe their noses with their hands, thereby
transforming hands into a vehicle for spreading disease to other
parts of the body and to other humans. Even adults may
unconsciously spread organisms in this way. Some attempts have been
made to address MRSA and other gram-positive organisms in the nares
via a treatment agent. An example of such an agent is mupirocin
(Bactroban, Glaxo-SmithKline, Beacham Pharmaceuticals,
Philadelphia, Pa.). This antibiotic has been reported to have some
efficacy against nasal MRSA when used as recommended, but the
efficacy is dependent upon the susceptibility or resistance of the
particular strain of MRSA to mupirocin. The recommendation is that
the agent be used for short courses (application to the anterior
nares twice daily for five days). The preparation is provided as 2%
mupirocin calcium in a cream or ointment base for nasal
application. It should be noted that mupirocin has not been
approved for use in children under the age of 12.
[0013] However, mupirocin therapy has led to the development of
antibiotic resistance in patients. In some cases, the development
of resistance has been rapid and the resistance may become
problematic, especially when the product is used prophylactically.
See B. D. Cookson, "The emergence of mupirocin resistance: a
challenge to infection control and antibiotic prescribing
practice," Journal of Antimicrobial Chemotherapy (1998) 41,
11-18.
[0014] There is a continuing need for novel, safe and effective
treatment compositions which will eliminate or reduce carriage of
gram-positive pathogens in nares, wounds, and other loci of
colonization on the human body.
DETAILED DESCRIPTION OF THE INVENTION
[0015] Nasal, skin and wound formulations for the eradication or
substantial reduction of gram-positive organisms are now
disclosed.
[0016] In a preferred embodiment for topical application to the
skin and wounds, the formulation comprises a synergistic mixture
of: one or more aliphatic alcohols having nine to twelve carbons,
most preferably dodecanol; a fatty acid glycerol ester, most
preferably selected from the group consisting of glycerol
monolaurate, glycerol monocapric acid, glycerol monocaprylate and
mixtures thereof, and an organic acid, preferably selected from the
group consisting of benzoic acid or benzoic acid analogs, lactic
acid, mandelic acid or malic acid, and acetic acid, most preferably
benzoic acid or a benzoic acid analog.
[0017] In an alternative formulation for application to skin,
wounds and/or the anterior nares, the formulation comprises a
combination of an aliphatic alcohol having nine to twelve carbons,
most preferably dodecanol, in an amount of 10% or less of said
formulation, and a fatty acid glycerol ester, most preferably
selected from the group consisting of glycerol monolaurate,
glycerol monocapric acid, glycerol monocaprylate, and mixtures
thereof.
[0018] The preferred C9-C12 aliphatic alcohol ingredient of the
formulation has been reported as having activity against bacteria
in vitro. However, these alcohols have not been employed in a
method for eradicating MRSA bacteria on skin. In particular, there
has been no known teaching of application to open wounds, or the
anterior nares. Although such alcohols have been listed as toxic or
otherwise dangerous when applied to the human body at some
concentrations, dodecanol has been used at very low concentrations
as an emollient in cosmetic preparations. It has now been found
that when used in combination with the other components of the
novel formulation, the concentration of dodecanol can be lowered
below the amount heretofore thought to be irritating, while still
maintaining efficacy of the formulation against MRSA bacteria.
[0019] It has been found that a low concentration of C9-C12
aliphatic alcohol in combination with a fatty acid glycerol ester
is effective in eliminating or greatly reducing the concentration
of MRSA S. aureus upon topical application to an area of the human
body in which said bacteria is residing. Increased efficacy is
achieved by pairing said aliphatic alcohol with a fatty acid
glycerol ester, most preferably selected from the group consisting
of glycerol monolaurate, glycerol monocapric acid, glycerol
monocaprylate and mixtures thereof. The concentration of C9-C12
aliphatic alcohol is from about 25 micrograms/mL to about 0.05
grams/mL. The concentration of said fatty acid glycerol ester is
from about 20 micrograms/mL to about 0.05 grams/mL.
[0020] Another embodiment of the invention is a method for treating
the nares with a formulation capable of achieving a greater than
seven or greater than eight log kill of gram-positive bacteria in
vitro in one minute or less. In this method, the formulation
comprises a C9-C12 aliphatic alcohol in a concentration from about
100 micrograms/mL to about 0.05 grams/mL and a fatty acid glycerol
ester in a concentration from about 125 micrograms/mL to about 0.05
grams/mL.
[0021] In a preferred embodiment, a method for treating nares, skin
or wounds with a formulation comprising a C9-C12 aliphatic alcohol,
a fatty acid glycerol ester and an organic acid which together
provide a synergistic effect is disclosed. The concentration of
each component can be lowered as compared with the two-component
formulation of the invention due to this synergism. Each component
can be lowered to a concentration that is one-fourth or less of the
component's individual MIC and still remains effective at
eradicating the MRSA organisms. Effective ranges for the components
are: dodecanol 20 micrograms to 5.0 grams; glycerol monolaurate 15
micrograms to 5.0 grams; and benzoic acid 250 micrograms to 4.0
grams per 100 grams of ointment base. A preferred amount of benzoic
acid is about 2 grams per 100 grams of ointment base.
[0022] In another embodiment, additional components may be added to
the formulation when it is intended for the treatment of wounds or
catheter sites. Components, such as phenyl ethyl alcohol and acetic
acid, which are known in the art to inhibit the growth of
gram-negative bacteria, may be included. Components, such as acetic
acid or zinc pyrithione, which help to prevent colonization by
yeasts and molds, may also be included in preparations intended to
be used on catheter sites. A preferred amount of acetic acid is 3%.
A preferred amount of zinc pyrithione is 0.25%.
[0023] In yet another embodiment, the formulation may be used as an
adjuvant to existing over-the-counter (OTC) antibiotic preparations
such as those containing neomycin, Polymyxin B and Bacitracin, or
their combinations. For example, the formulation of the invention
can be added to Bacitracin intended for application to the anterior
nares and the ability of the combined agents to eradicate MRSA will
be greatly increased.
[0024] The formulation as an adjuvant may also be added to
antiseptic preparations and alcohol gels containing short-chain
aliphatic alcohols in concentrations greater than fifty percent by
volume. In this application, the formulation provides an
antibacterial enhancing agent for these preparations, increasing
the effectiveness of treatment to include gram-positive bacteria,
as well as MRSA.
Formulation of Novel Ointment for MRSA Eradication in the Nares
[0025] A preferred formulation comprises an aliphatic alcohol such
as dodecanol, a fatty acid glycerol ester such as glycerol
monolaurate, and a benzoic acid analog such as benzoic acid, along
with a carrier base which adapts to mucus membrane adherence.
[0026] A representative formulation is exemplified below.
Example Formula I
TABLE-US-00001 [0027] Ingredient Amount/100 grams Function
Petrolatum 55.0 grams Carrier base and emollient Propylene glycol
10.0 grams Carrier base and emollient Polawax 15.0 grams Emulsifier
Dodecanol 5.0 cc Antimicrobial and penetrating agent Glycerol 5.0
grams Antimicrobial and monolaurate emollient Benzoic acid 2.0
grams Antimicrobial Eucalyptus oil 2.0 cc Odorant Water, DI 6.0
grams Diluent
[0028] To prepare the novel ointment of this invention, petrolatum
and Polawax are heated slowly to melt the products. Proylene glycol
is added to the liquified petrolatum and Polawax with stirring to
produce a homogenous mixture. The medium-chain alcohol(s), fatty
acid ester(s), benzoic acid, eucalyptus oil and water are added and
stirred to produce a homogenous mixture. While slowly stirring, the
solution is allowed to return to room temperature.
[0029] An alternative representative formulation is exemplified
below.
Example Formula II
TABLE-US-00002 [0030] Ingredient Amount/100 grams Function PEG 400
80 grams Carrier base and emollient PEG 3350 12.5 grams Carrier
base and emollient Dodecanol 4.0 grams Antimicrobial and
penetrating agent Glycerol 3.0 grams Antimicrobial and monolaurate
emollient Benzoic acid 0.50 grams Antimicrobial
[0031] To prepare the alternative formulation of the novel ointment
of this invention, PEG 3350 is heated slowly to melt the product.
The PEG 400 is added to the PEG 3350 and stirred to produce a
homogenous solution. The medium-chain alcohol(s), fatty acid
ester(s) and benzoic acid are added and stirred to produce a
homogenous solution. While slowly stirring, the solution is allowed
to return to room temperature.
[0032] The aliphatic alcohol of the formulation is selected so that
it can be employed at a concentration and pH compatible with
contact with the mucous membranes or open wounds. The appropriate
pH of the product will depend upon the application site. The pH may
be lowered to 4.0 for products applied to the squamous epithelium
that covers the distal nares (vestibule). For wounds, it is
preferable to keep the pH as near to 7.4 as possible.
[0033] The composition comprises an aliphatic alcohol, preferably
C9-C12, preferably C10-C12, and most preferably C12. Aliphatic
alcohols C10-C12 have been found to be effective at inhibiting
common strains of staphylococci, but not MRSA, at ranges of 12.5-50
micrograms/mL. Dodecanol (C12) specifically has been found to be
effective against Methicillin resistant S. aureus (MRSA),
Vancomycin intermediate S. aureus (VISA) and Vancomycin resistant
Enterococcus faecalis (VRE) at 83 micrograms/mL. See Table II
below.
[0034] The formulation further comprises a fatty acid glycerol
ester. The fatty acid glycerol ester is selected from a group of
010-013 glycerol esters. The fatty acid glycerol ester is
preferably a glycerol monoester, preferably selected from the group
consisting of glycerol monolaurate, glycerol monocaprin and
glycerol monocaprylate. Most preferably, the glycerol monoester is
glycerol monolaurate.
[0035] The formulation further comprises an organic acid. The
organic acid is selected to be non-irritating to human tissues at
the concentration employed. The pH should be near 7.4 if applied to
a wound. Mineral acids, such as hydrochloric acid and sulfuric
acid, should be avoided. Acids of choice would be selected from
among benzoic acid and benzoic acid analogs, lactic acid, mandelic
acid, and malic acid. Most preferably, benzoic acid is employed as
the organic acid component.
[0036] The combination of an aliphatic alcohol, fatty acid ester,
and organic acid provides a formulation having antibacterial
activity that far exceeds the antibacterial activity of any
component employed alone, and it is demonstrated here that a
synergistic relationship exists between the three components. A
combination using each of the components at less than 25% of the
individual MIC concentrations was as effective against S. aureus
MRSA as the individual components at full concentration.
[0037] The formulation preferably further comprises a penetrating
agent. Use of a penetrating agent is preferred so that the
formulation may penetrate through dry crusty material which may be
found inside the nasal cavity, thus permitting the antimicrobials
better contact with the affected nasal tissues and mucous
membranes. The penetrating abilities would also benefit in the
treatment of wounds, which may also be covered with crusty material
or scabs, allowing the formulation to reach the deeper layers of
the wound which may be colonized with MRSA.
[0038] It has been found that the aliphatic alcohol dodecanol not
only can be used as one of the synergistic components of the
formulation, but that it has dual activity as a penetrating agent.
The inclusion of an additional preferred penetrating agent, such as
lecithin phosphate at concentrations up to 20% (available from
HUMCO, Texarkana, Tex.), may be advantageous when the formulation
will be used on wounds. Isopropyl myristate, at a concentration of
2%, is another preferred penetrating agent which may be used. Many
other permeation enhancers are known in the art which could also be
used in the formulation, including polar solvents, and amphiphilic
compounds containing a polar head and a hydrophobic chain.
[0039] The formulation preferably further comprises one or more
components which provide an ointment base for the formulation. Care
must be taken to select base components which are compatible with
the active ingredients of the formulation for the particular
application. It has been found that some common ointment base
components may inhibit one or more of the active ingredients of the
formulation causing a decrease in the desired bactericidal
activity. Polyethylene glycols (PEG) are among the ointment bases
which may cause inhibition of bactericidal activity of the
formulation, possibly by causing bacterial cells to clump, and
therefore such components should be avoided. Preferred ointment
bases are petrolatum, propylene glycol, Polawax, and combination
thereof. Petrolatum and propylene glycol also have secondary uses
as emollient agents in ointment preparations. There may be specific
applications wherein PEG containing formulations are advantageous,
but for the nasal formulation, the use of petrolatum, propylene
glycol and Polawax in the ointment base is most preferred.
[0040] The formulation further comprises odorant compounds such as
eucalyptus oil. In addition to being a useful odorant for nasal
applications, eucalyptus oil is known to have antibacterial
properties. Other odorant compounds such as thymol and spearmint
may be added to certain embodiments of the formulation to increase
aesthetic appeal to the user.
[0041] The concentration of the ingredients may be higher when used
on intact skin or the anterior nares. The concentration should be
high enough in the anterior nares to achieve a seven to eight log
kill within one minute.
[0042] For use in wounds a formulation comprising lower
concentrations of the components may be used. Components of the
formulation would be metabolized following application to a wound
leading to a decrease in the amount of the formulation remaining in
the wound; however, the combination of the components would have a
residual bacteriostatic effect in the wound thereby preventing
recontamination.
[0043] The formulation of the invention is adapted for application
inside the human nares in a method of treatment to reduce or
eliminate S. aureus and/or other gram-positive pathogenic bacteria.
The perianal area is also a prevalent site for MRSA colonization
and this area could be treated with the formulation ointment
concurrently with treatment of the nares to insure complete
eradication of MRSA from both the nose and perianal areas of the
patient.
[0044] In one method, the formulation is applied to the anterior
nares. One application of the formulation effectively eradicates
all or nearly all of the gram-positive bacteria within one minute
of contact.
[0045] In another method of use, the treatment regimen includes
multiple applications to ensure eradication. One regimen comprises
the application of the formulation to the anterior nares every
twelve hours for three to five consecutive days.
[0046] The formulation may also be applied to the skin, or to
wounds and lesions located elsewhere on the body which may be
infected with gram-positive bacteria. For example, there are
multiple dermatoses which produce a disruption in skin integrity,
in which gram positive bacteria reside. A regimen comprises
application of the preparation to the wound or lesion site every
twelve hours until the infection has been eradicated.
[0047] In another embodiment, the active ingredients of the
formulation, dodecanol, glycerol monolaurate, benzoic acid and
eucalyptus oil, may be used in combination with other topical
antiseptics to produce a hand and body wash useful for the
eradication of MRSA from those body surfaces not treated with the
ointment formulation. Such a hand and body wash could be used as an
adjunct therapy to treatment of the nares and perianal regions in a
whole body MRSA eradication regimen.
[0048] In addition to the active ingredients of the formulation,
dodecanol, glycerol monolaurate, benzoic acid and eucalyptus oil,
components that help to prevent colonization by yeasts and molds,
such as acetic acid or zinc pyrithione, may also be included in
hand and body wash preparations. A preferred amount of acetic acid
is 3%. A preferred amount of zinc pyrithione is 0.25%.
[0049] A representative formulation for use as an alcohol-based
hand and body wash is described below.
Example Formulation III
TABLE-US-00003 [0050] Ingredient Amount/100 grams Function Ethyl
alcohol 68.42 cc Antimicrobial Emery 315 4.00 cc
Surfactant/conditioner Almond Oil 4.00 cc Emollient Medium chain
3.00 cc Emollient triglycerides Dodecanol 2.50 cc Antibacterial/
penetrating agent Glycerol monolaurate 2.50 grams
Antimicrobial/emollient Eucalyptus globules 2.00 cc Odorant Benzoic
acid 2.00 grams Antimicrobial Glycerin 2.00 cc Humectant/protectant
Lactic acid 2.00 cc Humectant/conditioner Vitamin E 2.00 cc
Antioxidant Spearmint 1.00 cc Odorant Klucel 1.00 cc Emulsion
stabilizer Thymol 0.50 grams Odorant DI Water 3.08 cc Diluent (Q.S.
to 100 cc)
[0051] One advantage of the formulation is that it is not subject
to the restrictions of antibiotic use previously discussed. The
formulations disclosed do not present a high risk of creating
strains with antimicrobial resistance, unlike antibiotics, said
antibiotics being naturally or synthetically derived from microbial
sources. One of the characteristics of the formulation is that it
comprises multiple antimicrobial components thus reducing the
possibility that resistance to any one component may occur. Another
characteristic of the disclosed formulation is the synergistic
effect that occurs when all three components, dodecanol, glycerol
monolaurate and benzoic acid, are used together thus allowing for a
smaller effective amount of each component to be employed.
[0052] Ingredients to enhance the aesthetic qualities of the nasal
ointment may be included into the formulation. These ingredients
may include odorants or additional emollients. While eucalyptus oil
is the preferred odorant for the formulation, odorants in addition
to eucalyptus oil may be employed. A preferred ingredient is 0.2%
eucalyptus oil.
Use of Aliphatic Alcohols in Formulation
[0053] Straight and branched-chain alcohols C9-12 are preferred.
The more preferred are straight-chain alcohols from C10-12. See
Table I below. The most preferred straight chain alcohol is
dodecanol (lauryl alcohol or 1-dodecanol). See Kubo, et al.
"Structural Functions of Antimicrobial Long-chain Alcohols and
Phenols." Bioorganic & Medicinal Chemistry (1995) Vol. 3 No. 7,
pp. 973-880.
TABLE-US-00004 TABLE I Effective Bactericidal Concentration of
Primary Alcohols against Staphylococcus (in Micrograms/mL) C-8 C-9
C-10 C-11 C-12 C-13 800 200 50 25 12.5 >800
[0054] Now reported are in vitro Minimum Inhibitory Concentrations
(MIC) for dodecanol against Staphylococcus aureus MRSA, ATCC 33591,
Staphylococcus aureus VISA (Vancomycin intermediate sensitivity)
ATCC 700699, and Enterococcus faecalis ATCC 51299 (formerly
Streptococcus faecalis VREF (vancomycin resistant)). One tenth of a
cc of dodecanol was diluted with 50 cc of polyethylene glycol 400
and 449.9 cc of sterilized deionized water, followed by five
doubling dilutions. The results are shown in Table II. The MIC for
dodecanol against the antibiotic-resistant strains tested is 83
.mu.g/mL. When combined with the other components of the
formulation, a synergistic effect is seen such that bactericidal
activity is still maintained even when the concentration of
dodecanol is reduced to 20 .mu.g/mL.
TABLE-US-00005 TABLE II Test Results for Dodecanol Final
Concentration (.mu.g/mL) Challenge Organism 83 41.5 20.25 10.125
5.0625 2.53125 MIC S. aureus 0 + + + + + 83 MRSA S. aureus 0 + + +
+ + 83 VISA E. faecalis 0 + + + + + 83 VRE Results expressed as
Growth (+) or No Growth (0) MIC = Minimum Inhibitory
Concentration
[0055] The example formulation above includes C12 (dodecanol). The
specific gravity of dodecanol is 0.83. Therefore, one cc weighs
0.83 grams or 830,000 micrograms. One cc in ten liters is still 83
micrograms/mL. At these low concentrations dodecanol has no
irritating effects on the mucous membranes.
[0056] As discussed above, dodecanol is also an effective
permeation enhancing agent promoting penetration into the affected
tissues while being physiologically acceptable for contact with
said tissues at the concentrations employed in the formulation
herein.
[0057] The preferred concentration of dodecanol is 0.0000001
percent to 5.0 percent. A more preferred concentration is 0.0001 to
2.5 percent. The most preferred concentration of dodecanol is 0.1
to 1.0 percent by volume.
Use of Glycerol Esters of Fatty Acids in Formulation
[0058] Fatty acids and their glycerol esters have been shown to
exhibit antimicrobial activity against a wide range of organisms,
including gram-positive bacteria. In addition, not only are these
glycerol esters of fatty acids not irritating to mucous membranes,
they provide an emollient effect on the treated tissue.
[0059] Several glycerol esters of fatty acids are available.
Monocaprin (glycerol monocaprylate) is a ten carbon fatty acid
ester. Monolaurate (glycerol monolaurate) is a twelve carbon fatty
acid ester. Dilaurin is the two carbon glycerol ester of lauric
acid. Tridecanoyl monoglyceride is the thirteen carbon fatty acid
ester. These fatty acid glycerol esters were tested in vitro for
activity against S. aureus to determine the Minimum Inhibitory
Concentrations (MIC) in micrograms/mL. The minimum inhibitory
concentrations in micrograms/mL of these glycerol esters of fatty
acids were tested in vitro for their activity against S. aureus.
The ten and twelve carbon forms have been proven to be effective
against MRSA. The results are in Table III. See Kabara, et al.
"Antimicrobial Lipids: Natural and Synthetic Fatty Acids and
Monoglycerides." Lipids (1977) Vol. 12 (9), pp. 753-759.
TABLE-US-00006 TABLE III Glycerol Esters of Fatty Acids Minimum
inhibitory concentration in micrograms/mL for Staphylococcus
Monocaprin Monolaurate Dilaurin 13 Carbon Mono 500 250 No
inhibition No Inhibition
[0060] Now reported are in vitro Minimum Inhibitory Concentrations
(MIC) for glycerol monolaurate against Staphylococcus aureus MRSA,
ATCC 33591, Staphylococcus aureus VISA (Vancomycin intermediate
sensitivity) ATCC 700699 and Vancomycin resistant Enterococcus
faecalis ATCC 51299 (formerly Streptococcus faecalis VRSF). The
results are shown in Table IV. The MIC for glycerol monolaurate
against the antibiotic-resistant Staphylococcus strains tested is
62.5 .mu.g/mL. When combined with the other components of the
formulation a synergistic effect is seen such that bactericidal
activity is still maintained even when the concentration of
glycerol monolaurate is reduced to 15 .mu.g/mL.
TABLE-US-00007 TABLE IV Test Results for Glycerol Monolaurate Final
Concentrationin micrograms/mL Challenge Organism 250 125 62.5 31.25
MIC S. aureus 0 0 0 + 62.5 MRSA S. aureus 0 0 0 + 62.5 VISA
Enterococcus 0 0 + + 125 faecalis Results expressed as Growth (+)
or No Growth (0). MIC = Minimum Inhibitory Concentration
[0061] Glycerol monolaurate is a lipophilic surfactant/emulsifier.
The exact mode of action for antibacterial activity against
gram-positive organisms is unknown but may involve effects on the
bacterial cell envelope or cell membrane. Another hypothetical mode
of action could be induction of autolysis activity.
[0062] Glycerol esters of fatty acids are not irritating to mucous
membranes. Glycerol monolaurate is the preferred fatty acid ester.
Glycerol monolaurate is available from Lauricidin, Inc. Galena,
Ill. A preferred concentration of glycerol monolaurate is 0.01% to
5.0%. A more preferred concentration of glycerol monolaurate is
0.01% to 5.0%. The most preferred concentration of glycerol
monolaurate is 0.1% to 5.0%.
Use of Benzoic Acid in Formulation
[0063] Benzoic acid is an organic acid which is a naturally
occurring derivative of benzene consisting of a carboxyl group
attached to a phenyl group. This acid has been found to exhibit
antibacterial activity against gram-positive bacteria while also
being non-irritating to tissues in the concentrations used in the
formulation.
[0064] The Minimum Inhibitory Concentration (MIC) for benzoic acid
was determined against Staphylococcus aureus MRSA. The results are
shown in Table V below. The MIC for benzoic acid against the
antibiotic-resistant strain tested is 1250 .mu.g/mL. When combined
with the other components of the formulation a synergistic effect
is seen such that bactericidal activity is still maintained even
when the concentration of benzoic acid is reduced to 312.5
.mu.g/mL.
TABLE-US-00008 TABLE V Challenge organism S. aureus MRSA Average
CFU/mL 8.9 .times. 10.sup.6 Benzoic Acid concentration 10,000 5,000
2,500 1,250 625 Tube .mu.g/mL .mu.g/mL .mu.g/mL .mu.g/mL .mu.g/mL
MIC Result 0 0 0 0 + 1250 .mu.g/mL Results expressed as Growth (+)
or No Growth (0)
Synergism of Formulation Components
[0065] It has now been found that, when combined, dodecanol,
glycerol monolaurate and benzoic acid exhibit a synergistic
antibacterial effect against gram-positive bacteria, specifically
MRSA. The MIC for dodecanol was experimentally determined to be
about 83 micrograms/mL, the MIC for glycerol monolaurate was
experimentally determined to be about 62.5 micrograms/mL, and the
MIC for benzoic acid was experimentally determined to be about 1250
micrograms/mL. The MIC results of the component combination are
shown in Table VI. When dodecanol was combined with a second
component, glycerol monolaurate, the minimum inhibitory
concentrations was experimentally determined to be about 40
.mu.g/mL for dodecanol and 30 .mu.g/mL for glycerol monolaurate,
thus demonstrating an additive antibacterial effect and that the
two components were not inhibited by each other. When a third
component, the organic acid benzoic acid, was added to the
formulation, the MICs for all three were much lower. As seen in the
table below, when the concentration of the dodecanol is 20 .mu.g/mL
and the concentration of glycerol monolaurate is 15 .mu.g/mL, the
benzoic acid can be decreased from its individual MIC of 1250
.mu.g/mL to 312.5 .mu.g/mL and the formulation still maintains full
bactericidal potency. The concentration of each of the components
can be reduced to less than one-fourth of the MIC for the
components individually while retaining full bactericidal potency
against MRSA, thus demonstrating unexpected synergism.
TABLE-US-00009 TABLE VI Synergism of Combination of Dodecanol,
Glycerol Monolaurate and Benzoic Acid Dodecanol (20 .mu./mL) and
Glycerol Monolaurate (15 .mu./mL) concen- trations held constant
with decreasing concentrations of Benzoic Acid Solution 1 Solution
2 Solution 3 Benzoic Acid Benzoic Acid Benzoic Acid Tube 1250
.mu.g/mL 625 .mu.g/mL 312.5 .mu.g/mL MIC Result 0 0 0 <312.5
.mu.g/ml Results expressed as Growth (+) or No Growth (0)
In Vitro Time-Kill Studies for Formulation Comprising Dodecanol and
Glycerol Monolaurate
[0066] Dodecanol and glycerol monolaurate were diluted to 2,000
micrograms/mL and then diluted to the following concentrations:
Dodecanol: 100 micrograms/mL and glycerol monolaurate: 250
micrograms/mL. Each challenge organism was confirmed by Gram stain
and colony morphology. The sterility controls exhibited no growth.
The resistance profile confirmation did not exhibit a zone of
growth inhibition when Staphylococcus aureus MRSA was exposed to an
oxacillin antibiotic disk thus confirming resistance. Log
reductions and percent reductions presented in Tables VII and VIII
below were calculated using the following equations:
Enumeration is expressed as colony - forming units ( CFU ) / mL .
Average Initial Controls minus Test Results Average Initial Count
of the Control Multiply .times. 100 = Percent Reduction Log (
Average Initial Counts Control ) minus Log Test Results = Log
Reduction ##EQU00001##
TABLE-US-00010 TABLE VII Initial Counts and Test Results for
Glycerol Monolaurate at 250 .mu.g/mL Initial Count 5.6 .times.
10.sup.6 CFU % Log Contact Time Recovered Reduction Reduction
Staphylococcus One Minute <5 .times. 10.sup.0 100 6.75 aureus
MRSA, ATCC 33591 Staphylococcus One Minute <5 .times. 10.sup.0
100 7.1 aureus VISA, ATCC 700699 Enterococcus One Minute <5
.times. 10.sup.0 100 7.04 faecalis ATCC 51299 Initial Count and
Test Results for Glycerol Monolaurate tested at 250 micrograms/mL
expressed as Average CFU per mL. Recovered. Percent and Log
Reduction.
TABLE-US-00011 TABLE VIII Initial Count and Test Results for
Dodecanol at 100 .mu.g/mL Initial Count 5.6 .times. 10.sup.6
Contact CFU Log Time Recovered % Reduction Reduction Staphylococcus
One Minute <5 .times. 10.sup.0 100 6.75 aureus MRSA, ATCC 33591
Staphylococcus One Minute <5 .times. 10.sup.0 100 7.18 aureus
VISA, ATCC 700699 Enterococcus One Minute <5 .times. 10.sup.0
100 7.04 faecalis ATCC 51299 Initial Count and Test Results for
Dodecanol tested at 100 micrograms/mL expressed as Average CFU per
mL. Recovered. Percent and Log Reduction
[0067] The log kill achieved in one minute by dodecanol, and
glycerol monolaurate is quite significant. It is foreseen that the
clinical application of each ingredient could achieve an
outstanding log kill when applied to mucous membranes or intact
skin to eradicate antibiotic resistant gram-positive organisms. The
effectiveness of glycerol monolaurate and dodecanol in achieving a
large log kill within a minute has been unknown until now. The
time-kill results from previous work would suggest that the
compounds would take as long as eight hours to be effective. The
log-kill was tested down to a time frame of one minute. An
outstanding seven log kill was obtained within one minute as seen
in the results above.
[0068] There have been reports that dodecanol can be irritating to
skin upon repeated exposure, however in the current invention it
has been found that the minimum inhibitory concentration of
dodecanol (83 .mu.g/mL) is well beneath the threshold where
irritation could occur. The concentration of dodecanol is further
reduced in the two-component formulation as used since there is an
additive effect between the dodecanol and the glycerol monolaurate
allowing the amount of dodecanol to be reduced to 40 .mu.g/mL. See
Table IX below. Further reduction of the dodecanol can be achieved
in the three-component formulation where addition of the benzoic
acid leads to a synergistic effect between the dodecanol, glycerol
monolaurate and benzoic acid, in which the effective concentration
of dodecanol can be further reduced to 20 .mu.g/mL, the
concentration of glycerol monolaurate reduced to 15 micrograms/ml
and the concentration of benzoic acid reduced to 312.5
micrograms/ml.
TABLE-US-00012 TABLE IX Additive Effect of Dodecanol and Glycerol
Monolaurate S. aureus MRSA - Average CFU/mL = 7.0 .times. 10.sup.6
Tested Concentration Result 40 .mu.g/mL Dodecanol 0 30 .mu.g/mL
Glycerol monolaurate 20 .mu.g/mL Dodecanol & + 15 .mu.g/mL
Glycerol monolaurate MIC 40 .mu.g/mL Dodecanol 30 .mu.g/mL Glycerol
monolaurate Expressed as Growth (+) or No Growth (0) MIC = Minimum
Inhibitory Concentration MIC for Dodecanol = 83 .mu.g/mL and MIC
for Glycerol monolaurate = 62.5 .mu.g/mL
[0069] The nasal formulation of the invention was tested against S.
aureus MRSA, ATCC 33591. The contact time for the formulation with
the bacteria was one minute, after which time, an 8.3 log reduction
in bacterial count was observed. The results are presented in Table
X below.
TABLE-US-00013 TABLE X Efficacy of Nasal Formulation against MRSA
Staphylococcus aureus MRSA, ATCC 33591 Initial Count 1.2 .times.
10.sup.9 Test Recovered Percent Log.sub.10 Test Agent Replicate
(CFU/mL) reduction reduction MRSA 1 <5 .times. 10.sup.0
>99.99 >8.38 Nasal 2 <5 .times. 10.sup.0 >99.99
>8.38 Formulation Active ingredients in MRSA Nasal Formulation:
dodecanol, glycerol monolaurate, benzoic acid, eucalyptus oil &
propylene glycol.
[0070] The hand and body wash formulation of the invention was
tested against S. aureus MRSA, ATCC 33591 and MDR Klebsiella
pneumoniae ATCC CI-2004. The contact time for the formulation with
the bacteria was one minute, after which time, an 8.3 log reduction
in bacterial count was observed for S. aureus and an almost
seven-log reduction was observed for K. pneumoniae. The results are
presented in Table XI below.
TABLE-US-00014 TABLE XI Efficacy of Hand and Body Wash against
Resistant Bacteria Test Agent Test Percent Log.sub.10 (CFU/mL)
Replicate Recovered reduction reduction Staphylococcus aureus MRSA,
ATCC 33591 Initial Count 1.8 .times. 10.sup.9 Eucalyptol 1 <5.0
.times. 10.sup.0 >99.99 >8.56 Hand and 2 <5.0 .times.
10.sup.0 >99.99 >8.56 Body Wash MDR Klebsiella pneumoniae
ATCC CI 2004 Initial count: 3.9 .times. 10.sup.7 Eucalyptol 1
<5.0 .times. 10.sup.0 >99.99 >6.89 Hand and 2 <5.0
.times. 10.sup.0 >99.99 >6.89 Body Wash Active ingredients in
MRSA Hand & Body Wash: ethyl alcohol, dodecanol, glycerol
monolaurate, benzoic acid & eucalyptus oil
Examples of Successful Treatment of MRSA Lesions Using the Novel
Formulations of the Invention are Provided Below
Example 1
[0071] A male, age 20, was diagnosed with a MRSA abscess
approximately 11/2 cm in circumference, located above the left
eyebrow. He did not use any oral antibiotics or antibiotic
ointments prior to applying the formulation ointment comprising
dodecanol and glycerol monolaurate directly to the abscess. The
subject applied the ointment directly to the wound two times for
two days, a total of 4 treatments. The third day after the first
application of the ointment, the abscess and any sign of pus or
infection had disappeared.
Example 2
[0072] A female, age 51, the mother of the patient referenced in
Example 1, discovered a small abscess on her right cheek. The
abscess and surrounding area was treated with the formulation
ointment comprising dodecanol and glycerol monolaurate. All signs
of infection were in remission the day following treatment.
Example 3
[0073] A male, age 78, was diagnosed with multiple MRSA abscesses
on his right index, ring and middle fingers. The patient was under
his doctor's care and received several antibiotics, both topical
and systemic. After three weeks the patient showed no improvement
and his case worsened. The patient was provided with the
formulation ointment comprising dodecanol and glycerol monolaurate
and instructed to treat his nose as well as to topically treat the
abscesses with the formulation ointment. Within a week all the
abscesses were dry and free of infection.
Example 4
[0074] A female, age 12, was diagnosed with MRSA. The abscess was
located on the left side of the patient's posterior. The patient
received several types of antibiotics and creams over a period of
two and half weeks with no success. A physician drained the abscess
3 times, but the abscess increased in size eventually to 3
centimeters. Upon being treated with the formulation ointment
comprising dodecanol and glycerol monolaurate in the nares and
directly on the abscess, within four days the abscess decreased in
size and was dry and infection free.
Example 5
[0075] A male, age 38, the father of the patient referenced in
Example 4, spotted a small MRSA abscess on his left thigh. The
abscess was treated with the formulation ointment comprising
dodecanol and glycerol monolaurate and the ointment was also
applied to the nares. The next day the abscess was markedly
improved and the infection was remediated.
Example 6
[0076] A female, age 6, was diagnosed with a 1/2 cm MRSA abscess on
her right index finger. The patient had been prescribed an
antibiotic which after a week had shown no effect on the abscess.
The formulation ointment comprising dodecanol and glycerol
monolaurate was applied to the patient's wound and two days later,
the abscess was remediated.
Example 7
[0077] A female, age 21, had been plagued by recurring incidences
of MRSA for several years. MRSA lesions were present on her neck
and legs. Several of the abscesses were drained and due to the
size, stitches were necessary to close the wounds. The treatment of
choice was mupirocin which was applied topically and in the nose.
Nose cultures were taken and the MRSA was still present in the
patient's sinuses. Prior to application of the formulation
ointment, she had been treated for MRSA on six different occasions
including with oral antibiotics. A pea-sized abscess was treated
with the formulation ointment comprising dodecanol and glycerol
monolaurate directly in the wound and in the nose and the lesion
disappeared within two days.
Example 8
[0078] A female, age 29, had an abscess on the lower right side of
her left breast. The abscess was about the size of a pea and was
identified as MRSA. The patient was unsuccessfully treated with
mupirocin. The abscess grew to the dimension of a half dollar coin.
The patient began using formulation ointment comprising dodecanol
and glycerol monolaurate on the wound and in the nares. On the
morning of the third day, the redness and pus had decreased. By the
fourth day, the wound was dry and visible signs of infection were
gone.
Example 9
[0079] A hospitalized male patient had a persistent problem with
MRSA contamination at the site of an in-dwelling catheter, a
peripherally inserted central line (PICC), which had been
non-responsive to treatment. The site was treated using the
formulation ointment comprising dodecanol, glycerol monolaurate,
and benzoic acid resulting in complete clearing of the MRSA from
the site.
Example 10
[0080] A child presents with MRSA in the nares. A formulation
ointment comprising benzoic acid, glycerol monolaurate and
dodecanol is applied to the nares of the patient. The dodecanol
component assists in penetrating the crust inside the nose and
synergistically acts with the glycerol monolaurate and benzoic acid
to reduce or eliminate MRSA organisms resident in the nares.
Transfer of MRSA from the nares to the skin is thus prevented,
thereby preventing contamination and possible skin lesions.
Example 11
[0081] A 12 year old child presents with recurrent impetigo of the
left cheek. The lesions were treated with the MRSA ointment three
times a day for one week with resolution. The anterior nares were
also treated prophylactically twice a day for three days.
Example 12
[0082] Patients presenting for surgical procedures can be treated
prophylactically with the formulation of the invention including
the nasal and perianal ointment plus the alcohol-based hand and
body wash formulation. Patients undergoing those procedures which
have a high incidence of post-surgical colonization with MRSA, such
as hip and knee replacement, cardiovascular surgery and
neurological surgery, as well as immunocompromised patients, such
as those with diabetes, AIDS or who are undergoing chemotherapy,
would especially benefit from such treatment.
Example 13
Skin Wash Compositions
[0083] An adjuvant composition comprising one or more aliphatic
alcohols having nine to twelve carbons, a fatty acid glycerol
ester, most preferably selected from the group consisting of
glycerol monolaurate, glycerol monocapric acid, glycerol
monocaprylate and mixtures thereof, and an organic acid, preferably
selected from the group consisting of benzoic acid or benzoic acid
analogs, lactic acid, mandelic acid or malic acid, most preferably
benzoic acid or a benzoic acid analog can be added to alcohol-based
hand and body washes, liquid hand soap or skin-washes based on
iodophoric compounds, for example povidone-iodine, and the like for
application to surfaces of the body which may be colonized or
contaminated with MRSA. Additional agents that can be employed in
the alcohol-based hand and body washes are persistent agents, most
preferably selected from zinc pyrithione, chlorhexidine and
triclosan.
Example 14
Pre-Surgery Prophylactic Use
[0084] Post-operative infections due to MRSA can be catastrophic to
patients following orthopedic, cardiovascular or central nervous
system procedures. Patients colonized in the anterior nares with
MRSA would benefit from the elimination of this organism to prevent
the risk of post-operative infection. This could easily be achieved
by applying the novel formulation of the invention to the anterior
nares prophylactically in the days prior to surgery. In addition,
the patient should use the alcohol-based hand and body wash for
three consecutive days prior to surgery.
Example 15
Dialysis Centers
[0085] Dialysis centers have become major sources of MRSA
infection. Patients, patients' family members and/or the healthcare
personnel could be treated with the nasal formulation and/or skin
wash compositions in order to eliminate the devastating effects of
MRSA in patients undergoing dialysis treatment, particularly those
with end stage renal disease.
Example 16
Hospitals and Nursing Homes
[0086] Hospitals and chronic long-term care facilities, including
nursing homes, often have patients who are colonized with HA-MRSA
in the anterior nares. These patients can spread the MRSA organism
via their hands to their caretakers, and when hospitalized for
acute illnesses, these patients may also transfer the organism to
other healthcare personnel and their patients. A nasal formulation
according to the invention can be applied to patients upon their
presentation to the emergency room or to admittance in order to
reduce spread of MRSA to others in the facility. Additional
treatments may be added as needed.
Example 17
Wound Treatment
[0087] The formulations for wound treatment described herein may be
applied directly to wounds such as post operative surgical wounds,
leg ulcers, pressure ulcers, diabetic ulcers, graft and donor
sites, partial thickness burns and/or traumatic wounds. For
treatment of wounds an anesthetic ingredient, such as 2% Xylocaine,
may be added to assist in pain management.
* * * * *